Gut microbiome-mediated transformation of dietary phytonutrients is associated with health outcomes.

Summary

Using integrated enzymatic, dietary and metagenomic resources across 3,068 human microbiomes, the authors mapped enzymes that transform 775 plant phytonutrients and showed large interpersonal/geographic variability. Enzyme abundance profiles predicted health status across diseases, and in vitro and mouse models linked these enzyme capacities to anti-inflammatory effects of foods.

Key Findings

• Mapped gut microbial enzymes responsible for transforming 775 plant phytonutrients across 3,068 human microbiomes.
• Demonstrated substantial interpersonal and geographic variability in phytonutrient biotransformation potential.
• Machine learning models using enzyme abundances discriminated health status across 2,486 case-control metagenomes.
• In vitro assays (e.g., Eubacterium ramulus) and gnotobiotic mouse metagenomics/transcriptomics linked enzyme capacity to anti-inflammatory activity of foods.

Clinical Implications

While not a clinical trial, the enzyme signatures could inform diagnostics and personalized diet prescriptions in metabolic and inflammatory disorders, and guide development of pre/probiotics targeting specific transformations.

Limitations

• Observational associations in human datasets limit causal inference for disease outcomes
• Food intake and diet context are inferred rather than controlled clinical exposures

Future Directions

Prospective interventional trials testing diet designs guided by microbiome enzyme profiles; development of targeted probiotics or enzymes to modulate specific phytonutrient transformations.